This investigation evaluated bacteriological activities, human pharmacokinetic profile and therapeutic effects of sulfamethoxazole (SMX) and trimethoprim (TMP) in combination.
Bacteriological : Antibacterial activities of SMX and TMP, alone and in combination were studied in clinically isolated strains; Staphylococcus aureus, Escherichia coli, Klebsiella and Proteus organisms. The potentiation of activities by combination in vitro was demonstrated in 29 of the 30 strains of Staphylococcus aureus, 22 of the 24 strains of Escherichia coli, 14 of the 18 strains of Klebsiella and 5 of the 9 strains of Proteus organisms.
Pharmacokinetic : Three healthy adults received a single oral dose of 2 tablets of SMX-TMP combination product (400 mg SMX and 80 mg TMP per tablet). Drug concentrations in the serum specimens, 2-6 hours following the drug administration ranged between 40 and 50 mcg/ml for free SMX and 1. 24-4.5 mcg/ml for TMP. The concentrations of free SMX in the serum was approximately 20 mcg/ml and that of TMP averaged 0.47 mcg/ml at 12 hour post-dosing. The concentrations of free SMX in the urine during the first 12 hours remained approximately 250-300 mcg/ml and those of TMP in the range of 95-100 mcg/ml.
Clinical : SMX-TMP combination product was therapeutically tried in 16 patients. Of these 16 patients, excellent response was achieved in 5, effective response in 7 and no response in 3. A trial in 1 patient was judged as not evaluable. Of interest was the response of 3 patients with serious pulmonary infections, 1 of these achieved remarkable response and the remaining 2 were satisfactory responders. Unwanted reactions included exanthema in 2 and anorexia in 1 patient.
